Unknown

Dataset Information

0

Galectin-3 enhances monocyte-derived macrophage efferocytosis of apoptotic granulocytes in asthma.


ABSTRACT: BACKGROUND:Galectin-3 is a 32?kDa protein secreted by macrophages involved in processes such as cell activation, chemotaxis and phagocytosis. Galectin-3 has previously been shown to improve the ability of airway macrophages to ingest apoptotic cells (efferocytosis) in chronic obstructive pulmonary disease (COPD) and may be of interest in non-eosinophilic asthma (NEA) which is also characterised by impaired efferocytosis. It was hypothesised that the addition of exogenous galectin-3 to monocyte-derived macrophages (MDMs) derived from donors with NEA would enhance their ability to engulf apoptotic granulocytes. METHODS:Eligible non-smoking adults with asthma (n?=?19), including 7 with NEA and healthy controls (n?=?10) underwent a clinical assessment, venepuncture and sputum induction. MDMs were co-cultured with apoptotic granulocytes isolated from healthy donors with or without exogenous recombinant galectin-3 (50??g/mL) and efferocytosis was assessed by flow cytometry. Galectin-3 expression and localisation in MDMs was visualised by immunofluorescence staining and fluorescence microscopy. Galectin-3, interleukin (IL)-6 and CXCL8 secretion were measured in cell culture supernatants by ELISA and cytometric bead array. RESULTS:Baseline efferocytosis (mean (±standard deviation)) was lower in participants with asthma (33.2 (±17.7)%) compared with healthy controls (45.3 (±15.9)%; p?=?0.081). Efferocytosis did not differ between the participants with eosinophilic asthma (EA) (31.4 (±19.2)%) and NEA (28.7 (±21.5)%; p?=?0.748). Addition of galectin-3 significantly improved efferocytosis in asthma, particularly in NEA (37.8 (±18.1)%) compared with baseline (30.4 (±19.7)%; p?=?0.012). Efferocytosis was not associated with any of the clinical outcomes but was negatively correlated with sputum macrophage numbers (Spearman r?=?-?0.671; p?=?0.017). Galectin-3 was diffusely distributed in most MDMs but formed punctate structures in 5% of MDMs. MDM galectin-3 secretion was lower in asthma (9.99 (2.67, 15.48) ng/mL) compared with the healthy controls (20.72 (11.28, 27.89) ng/mL; p?=?0.044) while IL-6 and CXCL8 levels were similar. CONCLUSIONS:Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.

SUBMITTER: Erriah M 

PROVIDER: S-EPMC6318889 | BioStudies | 2019-01-01T00:00:00Z

REPOSITORIES: biostudies

Similar Datasets

2019-01-01 | S-EPMC6747379 | BioStudies
1000-01-01 | S-EPMC6001567 | BioStudies
2018-01-01 | S-EPMC6174811 | BioStudies
2019-01-01 | S-EPMC6428974 | BioStudies
2019-01-01 | S-EPMC6581961 | BioStudies
2013-01-01 | S-EPMC3673667 | BioStudies
2010-01-01 | S-EPMC3992372 | BioStudies
2019-01-01 | S-EPMC6530174 | BioStudies
2012-01-01 | S-EPMC4030720 | BioStudies
1000-01-01 | S-EPMC5785262 | BioStudies